Itch Relief by Mirror Scratching. A Psychophysical Study.

OPEN 3 ACCESS Freely available online

PLOS I

Itch Relief by Mirror Scratching. A Psychophysical Study

Christoph Helmchen*, Carina Palzer, Thomas F. Miinte, Silke Anders, Andreas Sprenger

Department of Neurology, University of Luebecl<, Luebecl?, Germany

Abstract

Objective: The goal of this study was to test whether central mechanisms of scratching-induced itch attenuation can
be activated by scratching the limb contralateral to the itching limb when the participant is made to visually perceive
the non-itching limb as the itching limb by means of mirror images.

Methods: Healthy participants were asked to assess the intensity of an experimentally induced itch at their right
forearm while they observed externally guided scratch movements either at their right (itching) or left (non-itching)
forearm which were either mirrored or not mirrored. In the first experiment, a mirror placed between the participant's
forearms was used to create the visual illusion that the participant's itching (right) forearm was being scratched while
in fact the non-itching (left) forearm was scratched. To control visibility of the left (non-mirrored) forearm, a second
experiment was performed in which unflipped and flipped real-time video displays of the participant's forearms were
used to create experimental conditions in which the participant visually perceived scratching either on one forearm
only, on both forearms, or no scratching at all.

Results: In both experiments, scratching the non-itching limb attenuated perceived itch intensity significantly and
selectively in the mirror condition, i.e., when the non-itching forearm was visually perceived as the itching limb.

Discussion: These data provide evidence that the visual illusion that an itching limb is being scratched while in fact
the non-itching limb contralateral to the itching limb is scratched, can lead to significant itch relief. This effect might be
due to a transient illusionary intersensory perceptual congruency of visual, tactile and pruriceptive signals. "Mirror
scratching" might provide an alternative treatment to reduce itch perception in focal skin diseases with persistent
pruritus without causing additional harm to the affected skin and might therefore have significant clinical impact.

Citation: Helmchen C, Palzer C, Munte TF, Anders S, Sprenger A (2013) Itch Relief by Mirror Scratching. A Psychophysical Study. PLoS ONE 8(12):
e82756. doi:10.1371/journal. pone. 0082756

Editor: Susana Martinez-Conde, Barrow Neurological Institute, United States of America
Received January 9, 2013; Accepted Novembers, 2013; Published December 26, 2013

Copyright: © 2013 Helmchen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: No current external funding sources for this study.

Competing interests: Dr. Helmchen has received speaker honoraria from Thieme Verlag, Pierre Fabre Pharma, GlaxoSmithKline, and Henning
Arzneimittel. Dr. Helmchen serves as an editorial board member of Neuro-ophthalmology and Frontiers in Neuro-otology. Dr. Munte is section editor of
BMC Neuroscience, co-editor of Frontiers in Language Sciences and Zeitschrift fur Neuropsychologie and serves as an editorial board member of Clinical
Neurophysiology. This does not alter the authors' adherence to all the Cover Letter PLOS ONE policies on sharing data and materials.

* E-mail; christoph.helmchen@neuro.uni-luebeck.de

Introduction

itch can be defined as an unpleasant sensation that
provokes the desire to scratch the itching site. Itch is
attenuated by scratching. Many inflammatory skin diseases,
e.g. atopic eczema, elicit an Itch sensation [1] but patients must
not scratch the Itching skin rashes as skin inflammation might
deteriorate. Unfortunately, sustained Itch relief Is not always
achieved by standard drug treatment. Thus, there Is a strong
need for additional interventions In persistent pruritus.

Histamine reliably elicits itch and a flare by axon reflexes and
is therefore used in many experimental human models of Itch.
In Inflammatory skin lesions, histamine is physiologically
released by mast cells and activates unmyelinated peripheral
C-flbers and spinothalamic lamina I neurons [2-4]. Via
spinothalamic afferents these signals are transmitted to brain

regions that encode location and Intensity of somatosensory
sensations , i.e., the primary and secondary somatosensory
cortex [5], and valence. I.e., Insula and anterior cingulate cortex
(ACC) [6].

Under normal conditions, scratching immediately attenuates
Itch. It has been proposed that scratchlng-related Itch relief Is
best explained by spinal and supraspinal Interactions rather
than peripheral receptor-mediated mechanisms [7,8]. For
example, excitation of spinothalamic tract neurons by
stimulation of the primary afferents by histamine is attenuated
by scratching [9]. Itch relief can also be obtained by scratching
sites remote from the Itching site [10,1 1] suggesting that central
mechanisms may be involved In the control of Itch. Scratching
does not need to be conducted by oneself but can also
alleviate Itch when performed by somebody else at the Itching
or a remote skin area [7].

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Itch Relief by Mirror Scratcliing

Driven by clinical demands we sought to establish an
experimental condition in which the participant perceives a
visible tactile manipulation (scratching) of the non-itching limb
to occur on the affected limb. This Idea has also recently been
proposed In an abstract on phantom Itch patients [12].
Altschuler and Scott observed that some patients with itch in a
phantom limb noticed phantom itch relief by watching the
reflection of scratching on the corresponding Intact limb In a
mirror [13]. Research in recent years has indicated that
multisensory integration can lead to illusionary perceptions in
situations that do not normally occur in real-life [14]. For
example, observing a mirror image of one's own limb can lead
to the Illusionary perception that the mirrored limb is one's own
contralateral limb. A mirror box, placed vertically on the table in
front of a subject's hand, has been used to elicit synaesthesia
[15]. When amputees [16] or stroke patients [17] observe their
intact limb in a mirror box that is carefully placed parallel to
their phantom or paretic forearm this can lead to the illusionary
perception that their phantom hand has been resurrected or
that their paretic limb Is moving [18]. Mirror visual feedback had
also been applied to relieve pain In complex regional pain
syndrome (CRPS) type 1 [19]. Vision and touch may interact in
a way that objects viewed in a mirror are recoded as originating
from a location within perlpersonal space [20]. Perception In
such visuo-tactlle conflicts seems to be dominated by visual
cues [14]. These examples show that under some conditions,
the brain can be "fooled" by multisensory stimulation in a way
that stimulations are perceived that do not actually exist. This
may elicit visuo- tactile Illusions with regard to a person's self-
body schema [14,18,21].

In the current study we sought to extend these findings to the
perception of Itch attenuation. Unlike mirror visual feedback
therapy In motor recovery (e.g. stroke patients) we did not try to
elicit the visual Impression of bimanual movements but referred
sensations in the mirrored forearm. Mirror elicited sensations
felt on skin sites which are not physically stimulated. I.e.,
referred sensations, have been shown In several patient
groups, e.g. with stroke [22], CRPS [23], and patients with
anesthetic limbs [24]. if CRPS type 1 patients observed tactile
stimulations of the mirrored image of their unaffected hand in
the mirror they felt allodynia on their affected hand [23].
Stimulation of the unaffected limb elicited referred sensation In
the affected limb. In contrast to this aversive allodynia we were
looking for an itch-attenuating referred sensation.

We hypothesized that Itch relief can be obtained by
scratching the limb contralateral to the itching limb if the subject
is made to visually perceive the non-itching limb as the itching
limb by means of a mirror image. To test this hypothesis, we
asked healthy participants to rate the perceived Intensity of an
experimentally Induced, histamlne-assoclated Itch before and
after they observed externally guided scratch movements
either at their itching or their non-itching forearm. Two different
experimental approaches were used.

In the first (mirror) experiment, the visual illusion that the
participant's itching (right) forearm was being scratched [while
In fact the participant's non-itching (left) forearm was being
scratched] was elicited by means of a mirror, placed in
between the participant's left and right forearm. In the mirror

experiment, the participant was instructed to look into the
mirror. While this design has a simple and easy-to-implement
experimental set-up that makes it suitable for clinical
applications, visibility of the non-itching (left) forearm in the
mirror condition is not completely controlled. Thus, In order to
rule out that any itch attenuation observed in the mirror
condition was induced by visual perception of scratch
movements on the mirrored and the real left forearm, we run a
second (video) experiment. In the latter, unfllpped and flipped
real-time video displays of the participant's forearms were used
to create experimental conditions in which the participant
visually perceived scratching either on one forearm only, both
forearms, or no scratching at all. Very recently, video-mediated
mirroring of hands had been shown to induce referred
sensations equally powerful compared with mirror reflections
[25]. We will show that "mirror scratching", i.e., the visual
Illusion that an Itching limb Is being scratched while in fact the
non-Itching limb contralateral to the Itching limb Is scratched,
can - at least partially - attenuate Itch.

Methods

Participants

Twenty-six male right-handed healthy volunteers [age: 26.5
±4.5 (SD), range: 19-38 years] participated in the study. One
participant was excluded from the analysis, because of large
differences in itch intensity ratings between trials (> 3 standard
deviations). Five additional participants were excluded because
baseline itch ratings did not exceed 15 percent of maximal
conceivable, unbearable itch intensity (measured by numeric
rating scale, NRS, or visual analogue scale, VAS). All
remaining participants participated In both experiments. None
of them had a history of spontaneous Itching, allergy or
inflammatory skin disease Including atopic eczema, or
symptoms and signs of peripheral or central neurological
conditions. The study was approved by the Ethics Committee
of the University of Lubeck and was conducted In accordance
with the declaration of Helsinki. All participants gave written
informed consent before participation. The participant shown in
Figure 1 gave written informed consent for publication of the
photograph as outlined in the PLOS One consent form.

Itch induction

Histamlne-dihydrochlorlde (0.03 ml, 1%) was injected (BD
MIcrolance 3 skin needles) Into the dermal-epidermal junction
of the volar aspect of the right forearm where itch-sensitive C-
fibers terminate [26]. This elicited a red spot (diameter: 1.5 cm)
around the injection side. To prevent visual Identification of the
Itching side, both forearms were labeled with red color making
them visually indistinguishable. After an average latency of 25
sec, an itch sensation without pain sensation developed,
gradually increased to reach a maximum at approximately 60
sec after the Injection and remained stable for at least 5
minutes before it started to decrease. No participant reported
itch more than 12 minutes after the injection. In the first
experiment, histamine injection and scratching procedures
were performed twice In two Identical trials for each
experimental condition, separated by a 20 min Interval during

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Itch Relief by Mirror Scratching

Scratching non- Scratching
itching side (left) itching side (right)

^= itchi

itching side

S+ = pruriceptive match, i.e. scratching on the itching side

S- = pruriceptive mismatch, scratching on the non-itching side

V+ = visual perception that the itching side is being scratched

V- = visual perception that the non-itching or no side is being scratched

Figure 1. Design of the mirror experiment. The photos show the four conditions of the 2x2 factorial design. The two conditions
(A,B) with direct view on both forearms are shown in the top row. The two mirror conditions (bottom row) in which the participant
visually perceives the non-itching (left) forearm in place of the itching (right) forearm (C) and in which the subject's view on the
scratching of the itching (right) forearm is prevented by the mirror (D). The injection site is masked by red color patches at
homologue skin sites on both forearms to prevent visual identification of the itching forearm. The lightning symbol indicates the
itching (right) forearm. S-: scratching at the non-itching (left) forearm; S+: scratching at the itching (right) forearm; V-; visual percept
that the non-itching (left) forearm is being scratched; V+: visual percept that the itching (right) forearm is being scratched.

doi: 10.1371/joumal.pone.0082756.g001

which itch perception ceased. The second injection was given
2 cm distal to the first one. Data were pooled across the two
trials of each condition unless they differed significantly from
each other.

Scratch procedure

Scratching was applied on the participant's right or left
forearm by the investigator by using an L-shaped bendable
copper sheet (thickness: 1mm; width: 10mm; length: 130mm)
[7]. Scratching was performed with the buckled smaller end
with rounded edges using a force that slightly bended the

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Itch Relief by Mirror Scratching

copper sheet. This exerted a force of 100 ±5 g to the skin. The
experimenter took care to conduct 6 even strokes of 6 cm
length (each lasting 2.5s) immediately adjacent to the injected
site (or the corresponding area on the contralateral forearm).
Scratching was trained prior to the experiment and controlled
by a digital balance scale. Scratching was not applied directly
to the site of histamine injection in order to prevent peripheral
interactions at the terminals of itch fibers, instead scratching
movements were delivered to a site approximately 2 cm lateral
to the histamine injection site or the homologous site on the
contralateral, non-itching forearm.

Assessment of perceived itch intensity before and after
scratching

Itch intensity was rated by each participant before (TO, 60
seconds after injection) and immediately after scratching (T1 ,
within 5 seconds after scratching) using both a numeric (NRS)
and visual analogue scale (VAS) [27]. The scales ranged from
0 (no itch) to 100 (maximal conceivable, unbearable itch
intensity with an excessive urge to stop the experiment).
Participants were told that 10/100 represented a just noticeable
itch, 30/100 an annoying itch with the beginning urge to
scratch, 70/100 an imperative, still tolerable urge to scratch,
and 100/100 required immediate test stop unless scratching is
provided. As itch intensity before scratching (TO) was rated
differently between participants we used the change in itch
intensity from TO to T1 (rating difference, RD), i.e., differences
between ratings (T0-T1 ) rather than relative difference values
(in %) entered pre-post data in the result section. The next
scratching procedure according to the experimental design
(see conditions A-D in experiment 1 and a-h in experiment 2)
was performed after 30 sec, which was the interval after which
itch intensity reached its maximum again.

Study Design

Experiment 1: IVIirror Experiment. In the first experiment,
we used a 2 x 2 design with factors actual side of scratching [S
+ = scratching of the itching (right) forearm, S- =scratching of
the non-itching (left) side] and visually perceived side of
scratching [V+] = visual perception that the itching side is being
scratched; V- = visual perception that the non-itching left
forearm or no side is being scratched). The two mirror
conditions [S+V-] and [S-V+] were created by using a large
mirror which was placed vertically between the forearms of the
participant. He was instructed to look into the mirror which
allowed him to see the mirrored left forearm in the place of the
right forearm without seeing the left forearm directly. Sight of
the right (itching) forearm was completely prevented by the
mirror (Figure 1C,D).The condition [S-V+] Condition (C) was
critical in this experiment as it was intended to elicit itch relief
by making the participant visually perceive the scratched non-
itching (left) forearm as his itching (right), forearm. The three
other conditions (A, B, D) served as control conditions. They
controlled the perceived effect of itch attenuation by scratching
the itching right forearm (B) or the non-itching left forearm (A).
Condition (D) controlled for itch attenuation by scratching the
itching but not visible forearm. This elicited a visuo-tactile
mismatch as the perceived right forearm (mirrored left forearm)

was scratched without seeing it. Visual cues of the histamine-
induced inflammatory reaction should have been prevented by
masking the inflammation by red colored areas looking alike on
both forearms.

Please note that the sequence of conditions could not be
fully randomized because the mirror needed to be adjusted for
the conditions [S+V-] and [S-V+]. Thus, only the order of the
non-mirrored conditions [S+V+] and [S-V-] and the order of the
mirror conditions [S+V-] and [S-V+] were randomized.

Experiment 2: Video experiment. The second experiment
was run to control the participants' visual perception more
closely than it was possible in the first experiment. Note that
although participants in the mirror condition of the first
experiment were instructed to look into the mirror while being
scratched, they might have seen their left forearm both in the
mirror and on the table. This might have led to the visual
perception of being scratched at the mirrored and the real
forearm. In order to control the visual perception of the non-
itching (left) forearm in mirror conditions, we performed a
second experiment in which we showed the participant flipped
and unflipped real-time video displays of either forearm. This
created a total of eight experimental conditions (2 x 2 x 2), four
in which the itching forearm was being scratched (S+) and four
in which the non-itching forearm was being scratched (S-). In
two of these four conditions, the itching (right) forearm was
visually perceived by the participant as being scratched (V+), in
the other two the itching forearm was visually perceived as not
being scratched (V-). Finally, the non-itching (left) forearm was
also indicated as being scratched (/+) or being not scratched
(/-). The eight experimental conditions (S+ [V+/-]; S+ [V-/+]; S+
[V+/+]; S+ [V-/-]; S- [V+/-]; S- [V-/+]; S- [V+/+]; S- [V-/-]) are
shown in Figure 2. Table 1 illustrates each experimental
condition (a-h) in Figure 2 as both are presented in the same
order to make comparisons easier. According to out
hypothesis, the critical condition in this experiment was the
condition [S-] [V+/-], which was intended to create the visual
illusion that the participant's itching (right) forearm was being
scratched while in fact the non-itching (left) forearm was
scratched (similar to condition S- [V+] in the first experiment).
Notably, this condition [S-] [V+/-] had the additional constraint
that scratching of the non-itching forearm was not seen by the
participant. The order of conditions was pseudorandomized,
with 4 repetitions of each experimental condition. The
experiment was run in four blocks, each consisting of 8 trials.

During the experiment, participants lay supine on a
comfortable bed and observed their forearms online on a
monitor which was fixed 1 m in front of the participant's head.
Scratching by the investigator was grabbed by a camera
(Logitech® C310) which presented real-time displays (latency <
50ms) on the monitor screen by a custom program written in
Matlab® (R2012a, The Mathworks, Natick/MA). Due to the very
slow scratch movements there was no visible delay between
actual movement and the visual display on the monitor. The
participant's field of view was restrained to the monitor screen
by a surrounding black curtain (black chamber) preventing
penetration of light and other visual cues. Note that the
participant's field of view covered only the lower forearms

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Itch Relief by Mirror Scratching

Scratching non-
itching side (left)

non-mirrored

Scratching
itching side (right)

non-mirrored

e

S- [V-/+]

S+ [V+/-]

S- [V + /-]

mirrored (2 x left)

S+ [V-/+]

S- [V+ / +]

mirrored (

2 X right)

d

mirrored

(2 X left)

g

S+ [V-/-]

mirrored (

'2 X right)

'h

S+ [V+/+]

S- [V-/-]

2x4 factorial design (S=scratching with respect to the itching side; V=visual perception of scratching)
S + = pruriceptive match, i.e. scratching on the itching side
S - = pruriceptive mismatch, scratching on the non-itching side

V [+/-] = visual perception that the itching but not the non-itching side is being scratched

V [+/+]= visual perception that scratching is performed on both forearms

V [-/-] = visual perception that no forearm is being scratched

V [-/+] = visual perception that not the itching but only the non-itching side is being scratched
Helmchen et al. Fig. 2

Figure 2. Design of the video experiment. The subject's view on the real-time video displays in the eight different experimental
conditions is shown. As in the mirror experiment, the injection site is masked by red color patches at homologue skin sides on both
forearms to prevent visual identification of the itching forearm.

Scratching side is indicated by [S-] at the non-itching (left) forearm and by [S+], at the itching (right) forearm. The visual percept that
scratching is applied to the non-itching (left) forearm only is indicated [V-/+]; to the itching (right) forearm only [V+/-], to both
forearms [V+/+], or visual percept that no scratching is applied [V-/-] (see also Table 1). In the case of two visible forearms, one
forearm is flipped (mirrored), the other is visible at it is normally seen.

doi: 10.1371/joumal.pone.0082756.g002

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Table 1. Experimental conditions in the video experiment
showing mirrored and non-mirrored forearms while
scratching of the non-itching (left, S-) or the itching (right, S

+) side.

Scratching non-itching (left) side (S-)

Scratching itching (right) side (S+)

a)Both arms are not mirrored

e) Both arms are not mirrored

^both arms are shown (unflipped)

both arms are shown (unflipped)

— ^scratching on the left arm visible
[V-/+]

— ♦ scratching on right arm visible [V+/-]

b)Both arms are mirrored

f) Both arms are mirrored

—♦■both arms are shown (flipped)

— > both arms are shown (flipped)

— ^scratching visible on right arm [V+/-]

— > scratching on left arm visible [V-/+]

c) Only the left arm is mirrored

g) Only the left arm is mirrored

—>■ left arm is shown twice (flipped and

—>■ left arm is shown twice (flipped and

non-flipped)

non-flipped)

— * scratching of both arms visible [V+/+]

no scratching visible [V-/-]

d) Only the right arm is mirrored

h) Only the right arm is mirrored

— > right arm is shown twice (flipped and

— > right arm is shown twice (flipped and

non-flipped)

non-flipped)

— * no scratching visible [V-/-]

scratching of both arms visible [V+/+]

doi: 10.1371/joumal.pone.0082756.t001

(without hands, see Figure 2) malting it virtually impossible to
distinguish them.

Statistical analysis

Statistical analyses were performed with SPSS 20.0 (IBM
Inc. NY/USA). Rating differences (RD) on VAS and NRS were
computed within subjects. RD data were regarded as ordinal
data. For comparison of two conditions, Wilcoxon-Test was
used; in one-factorial analyses Friedman-Test was performed.
For multifactorial comparisons RD data were transformed into
ranks and analyses of variance (ANOVAs) were performed on
rank-transformed data [28]. Correlations were calculated by
Spearman-Rho-tests. The level of significance was set at a=
0.05 (two-tailed) for all tests.

Results

For both studies ANOVAs on rank-transformed ratings were
performed in order to estimate the impact of trial repetition. In
both experiments ANOVAS with factors condition and repetition
on VAS and NRS revealed no significant main effect of
repetition and no significant condition-by-repetition interaction
(all p > 0.86). Thus, the ratings were pooled across conditions
by taking their median. Median perceived itch intensity before
scratching was 28.75 on the VAS and 30.0 on the NRS in the
mirror experiment, and 42.5 on the VAS and 40.0 on the NRS
in the video experiment. There was no significant difference in
perceived itch intensity between the experimental conditions
prior to scratching.

Mirror experiment

In the mirror experiment, itch relief differed significantly
across the four conditions, both on the NRS (d.f. = 3, Chi^ =

40.0, p < 0.001, Figure 3] and on the VAS (d.f. = 3, Chi^ = 28.3,
p < 0.001). Itch relief, as expected, was significantly stronger in
the two conditions in which scratching was applied at the
itching (right) side (S+; Figure IB, D) than in the two conditions
in which scratching was applied to the non-itching (left) side
(S-, Figure 1A, C). Interestingly, scratching at the itching (right)
side elicited a larger itch relief under visuo-tactile congruency
[S+V+] (Figure IB) than under visuo-tactile incongruency [S
+V-] (Figure ID). Critically, when scratching was applied to the
non-itching (left) forearm, itch relief was significantly greater
when the non-itching (left) forearm was visually perceived as
the itching (right) forearm IS-V+] (NRS: 30, VAS: 36.8%, Figure
1C) then when the non-itching (left) forearm was perceived as
the non-itching (left) forearm [S-V-] (NRS: 20%, VAS: 22.2%,
Figure 1A).

Video experiment

As in the mirror experiment, itch relief in the video
experiment was significantly stronger in the conditions in which
scratching was applied at the itching (right) side, both for VAS
(18.5 ±2.7, mean of all 4 conditions e-h. Figure 2, Table 1) and
NRS (18.8 ±2.6) vs. VAS (1.1 ±1.2) and NRS (0.7 ±1.2; mean
of all 4 conditions a-d. Figure 2, Table 1), respectively (VAS: Z
= 3.7, p< 0.001; NRS: Z = 3.8, p< 0.001). Interestingly,
conditions S+ [V-/+] and S+ [V+/+] (Figure 2 f,h) showed a
trend to stronger itch relief than condition S+ [V-/-] and S+ [V
+/-] (Figure 2 e. Figure 3 lower panel). The latter was expected
to elicit strongest itch attenuation as it provides visuo-tactile
congruency at the itching site ("seeing and perceiving
scratches where it itches": S+ [V+/-]). More importantly, when
scratching was applied to the non-itching (left) forearm, itch
relief was strongest [(NRS: 17.9% (median), VAS: 26.1%
(median) (Figure 2b, Figure 3 lower panel, b)] when the non-
itching (left) forearm was visually perceived as the itching
(right) forearm S- [V+/-], as compared to all other conditions
with left-sided stimulation (<4%) (Figure 3). Thus, itch relief in
this condition S- [V+/-] corroborated the findings in the mirror
experiment S- [V+] (Figure 1C).

Discussion

The current study tested the hypothesis that "mirror
scratching", i.e., scratching a mirrored non-itching forearm, can
attenuate a circumscribed, experimentally induced itch. In line
with our hypothesis, we observed a significant attenuation of
itch by remote scratching only in an experimental condition in
which the participant visually perceived the forearm being
scratched as the itching forearm. Observing the non-itching
forearm being scratched without the visual illusion did not result
in itch reduction.

Central mechanisms of itch relief

Itch is an annoying and unpleasant but usually not painful
sensation which evokes the desire to scratch. The urge to
scratch is reflected in activations of brain regions engaged in
the processing of the sensory and affective / motivational
aspects of itch and premotor cortical areas involved in the
action preparation [29-32]. Limbic, ventral prefrontal and

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Itch Relief by Mirror Scratching

Mirror study

25 ■

20.

^ 10.

Scratching
side

non-itching (left) [S-]

itching (right) [S+]

\

Condition
label

A

c

B

D

Visual
^ perception

[V-]

1

[V+]

1

[V+]

1

[V-]

/

CO
01

"05

25-

20-

15-

10-

0-

Video study

1

1

Scratching
side

non-itching (left) [S-]

itching (right) [S+]

Condition
label

g

— I —

[V-/-]

Visual
perception

[V-/+]

[V+/+

[V+/-]

[V+/-]

[V-/-]

[V-/+]

[V+/+]

Helmchen et al. Fig. 3

Figure 3. Comparison of condition-related itch relief in both experiments. Average rating difference (RD) of itch intensity (=
itch relief) in the mirror (upper panel) and video experiment (lower panel) on the NRS (mean pre-post rating differences ± SEM). For
better identification experimental conditions are labeled by capital (mirror experiment, A-D) and small (video experiment, a-h) letters.
While the scratching side is shown above for the non-itching (left) [S-] and the itching right [S+] forearm, the visually perceived
forearm is indicated below: visual percept that scratching is applied to the non-itching (left) forearm only [V-/+]; itching (right) forearm
only [V+/-], to both forearms [V+/+], or visual percept that no scratching is applied [V-/-] (see also Table 1 ). In the case of two visible
forearms, one forearm is flipped (mirrored), the other is visible as it is normally seen. Corresponding conditions in the mirror and
video experiment are highlighted by the same colors (see also Table 2). *=p<0.05; **=p<0.01 , ***=p<0.005

doi: 10.1371/joumal.pone.0082756.g003

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Itch Relief by Mirror Scratching

Table 2. Correspondence of experimental conditions in
experiment 1 (A-D) and experiment 2 (a-h).

Scratching

Experimental condition

Right (itching) forearm [S+]

B (e) D (g)

Left (non-itching) forearm [S-]

A (a) C{b)

doi: 10.1371/joumal.pone.0082756.t002

ventral striatal activations are associated with the desire to
achieve itch relief by scratching [31,33]. Ventral prefrontal
cortex generates reward predictions and ventral striatum
activation is associated with motivational processing [34].
Scratch-related activations may reflect the - for a short term -
highly rewarding nature and often addictive behavioural
response of scratching [11]. Itch-related activation in the
anterior cingulate cortex [29,31,33] is reduced during
scratching which probably reflects inhibition of itch processing
[35]. Mechanical pinprick stimuli can reduce itch intensity not
only when they are applied adjacent to the itching skin site but
also when they are applied at the contralateral extremity [36].
Taken together, these findings strongly support the notion that
itch relief is partly under control of central neural processes.
However, in the current study, scratching at a remote site alone
did not result in itch relief. Significant itch relief by remote
scratching was observed only if the participant visually
perceived the limb being scratched as the itching limb. This is
in line with the observation that some phantom itch patients
have reported phantom itch attenuation by observing
scratching of their intact foot through a mirror [1 3].

Perceptual congruency and mismatch of multisensory
stimulation

In the current study, itch relief was strongest when the itching
forearm was actually being scratched [S+], irrespective of the
visual percept. This is in line with previous studies and
underlines the predominant role of tactile-pruriceptive
congruency ("feeling being scratched where it itches") in itch
relief. However, moderate but significant itch relief was also
observed in conditions with tactile-pruriceptive incongruence
[S-], when the itching forearm was visually perceived as being
scratched [V+] ("seeing being scratched where it itches").
Because in conditions with tactile-pruriceptive incongruence
itch relief is unlikely to be due to peripheral mechanisms, these
findings provide further evidence that central mechanisms play
a pivotal role in itch relief and that itch relief is partly
independent of somatosensory input from the periphery. This
raises the question what exactly led to the significant itch relief
observed under tactile-pruriceptive incongruence in the current
study?

One possibility is that visual-tactile enhancement might play
a role in itch relief. Previous studies indicate that visibility of
touch stimulation can improve tactile perception [37,38]. Thus,
one might speculate that particularly in the first experiment,
where visibility of the non-itching forearm was not completely
controlled, visual perception of being scratched at both
forearms in combination with actually being scratched at the

non-itching forearm led to visuo-tactile enhancement which in
turn led to itch relief although the itching site was in fact not
scratched. However, this possibility is ruled out by the second
experiment. Intriguingly, in that experiment we observed
significant itch relief only when the participant visually
perceived solely the itching forearm as being scratched (S-V
+/-). The visual percept that both forearms were being
scratched (S- V+/+) did not lead to significant itch relief. This
provides some evidence that itch relief under tactile-
pruriceptive incongruence in the current study was due to the
visual illusion that the itching forearm was being scratched (i.e.
"mirror scratching") and not simply to visuo-tactile
enhancement.

Bodily illusions can result from conflicting or ambiguous
multisensory information [14]. Self-attribution of sensory stimuli
to body limbs has been suggested to be mediated by
multisensory perceptual interactions [39] which may, for
example, be accomplished by (i) mirror images [15] or mirrored
visual feedback [25] of body limbs with conflicting visuo-tactile
information or (ii) simultaneous stimulation of an own and
artificial limb, e.g. in the rubber hand illusion.

Observing a limb in a mirror can lead to the illusion that the
mirrored limb is the contralateral limb if the mirror is oriented in
a way that the mirrored limb is in place of the contralateral limb.
A mirror box, placed vertically on the table in front of a subject's
hand, has been used to elicit synaesthesia [15]. Patients with
phantom limb perceptions placed their normal hands into a
mirror box and were asked to look into the mirror, thus creating
the illusion of observing two hands, while in fact they saw only
the mirrored image of the normal hand. When the normal hand
was touched while they were seeing its mirrored reflections
they noticed tactile, i.e. referred sensations on the phantom
hand. This intermanual referral of tactile sensations was
crucially dependent on visibility of the mirrored image.
However, our experiments differed from mirror box studies [15]
such that itch attenuation was only seen when the participant
visually perceived solely the itching forearm as being scratched
[S-[V+] in the mirror experiment,) and S- [V+/-] in the video
experiment] but not when both forearms were visible.

Therefore we suggest that the scratching sensation in our
study is probably transferred to the visually perceived itching
limb (although the non-affected limb was physically scratched)
and contributed to itch relief.

For several reasons mechanisms of itch relief by mirrored
visual feedback should not be confused with another bodily
illusion that has been extensively studied during recent years,
i.e. the rubber hand illusion [39-41]. In this illusion, a person
observes a rubber hand being touched in synchrony with
touches applied at their own, but visually hidden hand. Once
the rubber hand is spatially orientated as the person's real
hand, simultaneous stimulations at corresponding body sites
can create the illusionary perception that the rubber hand
belongs to one's own body. This illusion can be quite strong
including, e.g., the perception of fear when the rubber hand is
under threat [42]. First, we used a mirror and video-mediated
mirrored images to elicit visual illusions and to change sensory
perceptions. Second, itch relief was not achieved by
simultaneous tactile stimulations (no effect on observing both

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Itch Relief by Mirror Scratcliing

forearms). Ttiird, itcti attenuation does not result from
simultaneous stimulation of two (real and rubber) hands lying in
close vicinity and similar spatial orientation with respect to one'
own bodily references but it occurs despite the fact that tactile
stimulation (scratch) is opposite to the itching limb. We believe
that the effect requires that the participants visually perceived
their mirrored non-itching hand as their right itching hand which
is visually perceived as being scratched. Therefore, the
mechanisms of mirror visual feedback by intersensory
perceptual interactions are clearly different from the rubber
hand illusion.

All in all, we suggest that itch relief by "mirror scratching" as
observed in the current study may result from Inappropriate
integration and weighing of simultaneous, spatially coded,
multisensory (visual, tactile, pruriceptive) signals leading to a
transient intersensory perceptual congruency of visual, tactile
and pruriceptive signals. However, while both effects result
from an inappropriate integration of signals, the particular
neural algorithms underlying these misperceptions might be
distinctly different. The pattern of itch relief observed in the
current study suggests that multisensory vlsuo-tactlle-
pruriceptive integration in itch perception is governed by a
weighing process: tactile-pruriceptive congruency ("feeling
being scratched where it itches") led to stronger itch relief than
visuo-pruriceptive congruence ("seeing being scratched where
it Itches"). Exploring the neural mechanisms that underlie this
weighing will be a challenging task for future studies.

Potential clinical role

Itch Is a prevalent symptom of allergic and Inflammatory skin
disease. Patients must not scratch itching skin sites to prevent
deterioration. Conventional drug therapy of pruritus does often
not lead to satisfactory itch relief. The current study provides
evidence that partial itch relief might be achieved by "mirror
scratching", i.e., by creating the illusionary visual perception
that an itching limb is being scratched while in fact non-lesional
skin of the contralateral limb is being scratched. The use of
illusionary visual mirror feedback has successfully been used
to partially restore brain function: e.g. In after stroke [17,18,43],

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We demonstrated that relief of an experimentally elicited,
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Acknowledgements

The authors like to thank anonymous reviewers of this

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